Induction of protective anti-tumor immunity by gene-modified dendritic cells.
The context in which an antigen is presented shapes the nature of the immune response to that antigen and can result in B cell activation, T cell activation, or immune tolerance. To elicit anti-tumor immune responses, various cell types have been employed as cellular adjuvants with tumor antigens, and recently several groups have shown that dendritic cells (DCs), cultured with tumor lysates, tumor antigens, or peptides eluted from tumor cells, induced significant anti-tumor immunity in vivo. In all of these approaches, the DCs were pulsed with an exogenous source of antigen. An alternative method is to engineer DCs to express tumor antigens. We genetically modified DCs to express beta-galactosidase (beta-gal) as a surrogate tumor antigen and then tested the anti-tumor activity of the beta-gal+ DCs in mice against a beta-gal+ murine melanoma cell line. A single vaccination with the gene-modified DCs protected mice against a lethal dose of beta-gal-B16 melanoma cells and induced beta-gal-specific cytotoxic T lymphocytes. These results demonstrate that expression of tumor antigens by DCs is a potent method of inducing tumor antigen-specific responses in vivo.
McArthur
J G
JG
Department of Gene Therapy Applications, Cell Genesys Inc., Foster City, California 94404, USA.
Mulligan
R C
RC
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005818:Genetic Engineering; D007167:Immunotherapy; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D014612:Vaccines; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology
D000951:Antigens, Neoplasm; D014612:Vaccines; D001616:beta-Galactosidase